Dr. Sekine has been working on analyzing the molecular mechanisms underlying cellular responses to a variety of stresses including oxidative stress, endoplasmic reticulum stress, and metabolic stress. Using biochemical and cell genetic approaches, the Sekine Lab is currently focusing on acetyl-CoA fluctuation-dependent functional alterations in organelles (including nucleoli, mitochondria, and lysosomes) and activation of organelle-associated stress signaling pathways. A long-term goal is to understand the sensing mechanisms of metabolite fluctuations in cells and to reveal their relevance to human aging and age-associated diseases.
- BS, The University of Tokyo, 2005
- MS, The University of Tokyo, 2007
- PhD, The University of Tokyo, 2010
- Postdoctoral Fellow, The University of Tokyo, 2010
- Visiting Research Fellow, University of Cambridge, United Kingdom, 2013
- Research Fellow, National Institutes of of Health, Bethesda, 2016
Education & Training
Liu, J., Zuo, Z., Sastalla, I., Liu, C., Jang, J.-Y., Sekine, Y., Li, Y., Pirooznia, M., Leppla, S. H., Finkel, T., Liu, S. Sequential CRISPR-Based Screens Identify LITAF and CDIP1 as the Bacillus cereus Hemolysin BL Toxin Host Receptors. Cell Host Microb. 2020; 28: 402-410.e5.
Baumer, Y., Dey, A. K., Gutierrez-Huerta, C. A., Khalil, N. O., Sekine, Y., Sanda, G. E., Zhuang, J., Saxena, A., Stempinski, E., Elnabawi, Y. A., Dagur, P. K., Ng, Q., Teague, H. L., Keel, A., Justin A., Rodante, J.A., Boisvert, W. A., Tsoi, L. C., Gudjonsson, J. E., et al. Hyperlipidaemia and IFNgamma/TNFalpha Synergism are Associated with Cholesterol Crystal Formation in Endothelial Cells Partly Through Modulation of Lysosomal pH and Cholesterol Homeostasis. EBioMedicine. 2020; 59: 102876.
Houston, R., Sekine, S., Calderon, M. J., Seifuddin, F., Wang, G., Kawagishi, H., Malide, D. M., Li, Y., Gucek, M., Pirooznia, M., Nelson, A. J., Stokes, M. P., Stewart-Ornstein, J., Mullett, S. J., Wendell, S. G., Watkins, S. C., Finkel, T., Sekine, Y. Acetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses. PLoS Biol. 2020; 18: e3000981.
Zyryanova, A. F., Weis, F., Faille, A., Alard, A. A., Crespillo-Casado, A., Sekine, Y., Harding, H. P., Allen, F., Parts, L., Fromont, C., Fischer, P. M., Warren, A. J., Ron, D. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science. 2018; 359: 1533-1536.
Sekine, Y., Zyryanova, A., Crespillo-Casado, A., Amin-Wetzel, N., Harding, H. P., Ron, D. Paradoxical sensitivity to an integrated stress response blocking mutation in vanishing white matter cells. PLoS One. 2016; 11: e0166278.
Sekine, Y., Zyryanova, A., Crespillo-Casado, A., Fischer, P. M., Harding, H. P., Ron, D. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science. 2015; 348: 1027-1030.
Halliday, M., Radford, H., Sekine, Y., Moreno, J., Verity, N., le Quesne, J., Ortori, C. A., Barrett, D. A., Fromont, C., Fischer, P. M., Harding, H. P., Ron, D., Mallucci, G. R. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis. 2015; 6: e1672.
Mosallanejad, K., Sekine, Y., Ishikura-Kinoshita, S., Kumagai, K., Nagano, T., Matsuzawa, A., Takeda, K., Naguro, I., Ichijo, H. The DEAH-box RNA helicase DHX15 activates NF-kB and MAPK signaling downstream of MAVS during antiviral responses. Sci Signal. 2014; 7: ra40.
Sekine, Y., Hatanaka, R., Watanabe, T., Sono, N., Iemura, S., Natsume, T., Kuranaga, E., Miura, M., Takeda, K., Ichijo, H. The kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol Cell. 2012; 48: 692-704.
Sekine, Y., Takagahara, S., Hatanaka, R., Watanabe, T., Oguchi, H., Noguchi, T., Naguro, I., Kobayashi, K., Tsunoda, M., Funatsu, T., Nomura, H., Toyoda, T., Matsuki, N., Kuranaga, E., Miura, M., Takeda, K., Ichijo, H. p38 MAP kinase regulates the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors. J Cell Sci. 2011; 124: 3006-3016.
- Samuel and Emma Winters Foundation, 2020-2021
- UPMC Health System Competitive Medical Research Fund, 2020-2021
